TY  - CHAP
M1  - Book, Section
TI  - Overview
A1  - Pace, Betty S.
A1  - Brugnara, Carlo
A2  - Gladwin, Mark T.
A2  - Kato, Gregory J.
A2  - Novelli, Enrico M.
PY  - 2021
T2  - Sickle Cell Disease
AB  - This  section  highlights  the  pathophysiologic  complexity  of  sickle  cell  disease  (SCD),  the  prototype  of  single-gene  molecular  disorders.  James  Herrick  published  the  first  clinical  report  of  SCD  in  1910.  However,  many  decades  passed  before  Linus  Pauling  established  SCD  as  the  first  human  monogenic  disorder,  with  an  autosomal  recessive  inheritance  pattern,  in  1949.  This  seminal  work  laid  the  foundation  for  the  explosion  of  knowledge  in  human  molecular  genetics.  Over  the  past  few  decades,  the  pathophysiology  of  SCD  has  been  explored  and  clarified  in  many  aspects,  but  other  aspects  still  present  uncertainties  and  lack  of  detail.  The  molecular  mechanisms  of  the  process  leading  to  polymerization  of  hemoglobin  S  (HbS)  and  sickling  have  been  elucidated  in  extreme  detail,  and  this  knowledge  has  been  critical  in  rationalizing  the  beneficial  effects  of  several  of  the  novel  therapies  developed  or  under  development  for  the  disease.  It  has  also  become  clear  that  a  unique  feature  of  SCD  is  the  pathologic  involvement  of  multiple  organs  most  often  as  a  consequence  of  vascular/inflammatory  or  ischemia-reperfusion  complications  of  the  disease.  The  interactions  of  sickle  cells  with  the  endothelium  and  the  inflammatory  response  associated  with  the  disease  have  been  examined  in  a  variety  of  experimental  systems,  with  SCD  emerging  as  a  unique  model  of  ischemia-reperfusion  (I/R)  disorders.  These  studies  have  been  facilitated  by  the  development  of  transgenic  mouse  models  for  SCD,  which  recapitulate  disease  pathophysiology  and  provide  a  model  to  test  therapeutic  interventions.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/23
UR  - hemonc.mhmedical.com/content.aspx?aid=1179345988
ER  -